Heroin use is associated with significant medical and social problems. In addition to HIV and other blood-borne infections there is concern about mounting heroin-related overdose (HOD) and bacterial skin and soft tissue infections (SSTI) including methicillin-resistant staphylococcus aureus (MRSA) infections. Social concerns include trafficking-related violence and societal costs of heroin use eg incarceration and healthcare utilization. US heroin and illicit opioid supply and consumption are changing: in the past 20 years, as Colombian- sourced heroin gained dominance, heroin prices have decreased and purity increased to record levels; prescription opioid pill misuse has drawn in new populations that are younger, more rural, white and female. Nationwide heroin use is increasing dramatically due to robust availability of high quality heroin and a wave of dependent opioid pill users switching to this cheaper, more reliable supply. In addition the heroin supply is in flux wit evidence of sharply increased production in Mexico and a diversity of heroin products hitting US streets. What are the health and behavioral implications of use of these novel heroin source-forms? Different source-forms of heroin are chemically distinct leading to different use patterns and medical consequences. Distribution of Colombian-sourced powder heroin (PH), a cold-water soluble heroin, is associated with greater HIV and HOD. New forms of powdered heroin are emerging regionally eg chocomil, gunpowder, fentanyl-laced heroin and cheese heroin; all are cold water soluble raising concerns about increased HIV and HOD risk. In addition, some market characteristics, eg branding, maybe associated with higher quality heroin and more negative consequences than others. How are changes in heroin supply, heroin market structure and quality affecting populations at risk and healthcare utilization and costs? The Heroin in Transition study will investigate the rapidly evolving risk environment for heroin users in the US utilizing integrated micro- to macro-level anthropological, economic and epidemiological approaches. Specific Aim 1: To assess, through qualitative inquiry, the micro-personal risk behaviors of heroin IDUs related to their use of specific major and variant types of heroin in 2 sentinel and 12 rapid assessment sites. Specific Aim 2: To examine the structure of heroin markets and retail heroin price/purity in 27 US MSAs, 1993-2014, relating them to changes in populations at risk, healthcare utilization and societal costs. Specific Aim 3: To develop longitudinal and agent-based models linking heroin and opioid market conditions, ie structure, availability and quality, to individuals' patterns of heroin-related medical outcomes eg HIV, HOD, SSTI and MRSA.